JKB-121 for the Treatment of Nonalcoholic Steatohepatitis

December 7, 2018 updated by: Manal Abdelmalek

A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Phase II Trial of JKB-121 for the Treatment of Nonalcoholic Steatohepatitis (NASH)

To evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

JKB-121 is a long-acting small molecule that is efficacious as a weak antagonist at the TLR-4 receptor. It is a non-selective opioid antagonist which has been shown to prevent the lipopolysaccharide (LPS) induced inflammatory liver injury in a methionine/choline deficient diet fed rat model of nonalcoholic fatty liver disease. In vitro, JKB-121 neutralized or reduced the LPS-induced release of inflammatory cytokines, deactivated hepatic stellate cells, inhibited hepatic stellate cell proliferation, and collagen expression. Inhibition of the TLR4 signaling pathway may provide an effective therapy in the prevention of inflammatory hepatic injury and hepatic fibrosis in patients with nonalcoholic steatohepatitis. This study will evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
65

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Dothan, Alabama, United States, 36305
        • Digestive Disease Specialists of the Southeast
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School Of Medicine
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Digestive Associates
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Digestive Disease Specialists
    • Texas
      • Houston, Texas, United States, 78234
        • Brook Army Medical Center
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Health Systems
      • Richmond, Virginia, United States, 23298
        • Medical College of Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Provision of written informed consent
  3. Biopsy-proven NASH within 12 months or at screening
  4. ALT > 40 U/L for women and > 60 U/L for men at screening and at least once in the previous 12 months.
  5. HBA1C of ≤ 9.0

Exclusion Criteria:

  1. Any chronic liver disease other than NASH
  2. Cirrhosis, as assessed clinically or histologically
  3. Presence of vascular liver disease
  4. BMI ≤ 25 kg/m2
  5. Excessive alcohol use (> 20 g/day) within the past 2 years
  6. AST or ALT > 250 U/L.
  7. Type 1 diabetes mellitus
  8. Bariatric surgery in the past 5 years.
  9. Weight gain of > 5% in past 6 months or > 10% change in past 12 months.
  10. Contraindication to MRI
  11. Inadequate venous access
  12. HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or Hepatitis C virus (HCV) RNA positive.
  13. Receiving an elemental diet or parenteral nutrition
  14. Chronic pancreatitis or pancreatic insufficiency
  15. Any history of complications of cirrhosis

  16. Concurrent conditions:

    • Inflammatory bowel disease
    • Significant cardiac disease
    • chronic infection or immune mediated disease
    • Any malignant disease
    • Prior solid organ transplant
    • Any other concurrent condition which, in the opinion of the investigator, could impact adversely on the subject participating or the interpretation of the study data.
  17. Concurrent medications which may treat NASH
  18. HbA1C > 9.0%
  19. Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: A
JKB 121, 5 mg twice daily
Drug: JKB-121: 5 mg twice daily
Active Comparator: B
JKB 121, 10 mg twice daily
Drug: JKB-121: 10 mg twice daily
Placebo Comparator: C
Identical appearing placebo
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
Time Frame: Baseline to week 24
Baseline to week 24
Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)
Time Frame: Baseline to Week 12
Baseline to Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)
Time Frame: Baseline to week 24
Baseline to week 24
Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)
Time Frame: Baseline to week 12
Baseline to week 12
Time to Remission (in Weeks)
Time Frame: 24 weeks
Time to remission is the time in weeks from randomization to liver function remission, defined as two consecutive ALT values within normal range (<40 U/L) during the treatment period.
24 weeks
Change in BMI (Body Mass Index)
Time Frame: Baseline, week 24
Baseline, week 24
Change in Hemoglobin A1C
Time Frame: Baseline, week 24
Baseline, week 24
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Time Frame: Baseline, week 24
HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. Optimal Range: 1.0 (0.5-1.4). Lower values represent a better outcome.
Baseline, week 24
Percent Change in Cholesterol
Time Frame: Baseline, week 24
Baseline, week 24
Percent Change in Triglycerides
Time Frame: Baseline, week 24
Baseline, week 24
Percent Change in Low Density Lipoprotein (LDL) Cholesterol
Time Frame: Baseline, week 24
Baseline, week 24
Percent Change in High Density Lipoprotein (HDL)
Time Frame: Baseline, week 24
Baseline, week 24
Mean Serum Aspartate Aminotransferase (AST)
Time Frame: weeks 4, 8, 12, 16, 20, and 24
weeks 4, 8, 12, 16, 20, and 24
Mean Serum Alanine Aminotransferase (ALT)
Time Frame: weeks 4, 8, 12, 16, 20, and 24
weeks 4, 8, 12, 16, 20, and 24
Mean Serum Gamma-glutamyl Transpeptidase (GGT)
Time Frame: weeks 4, 8, 12, 16, 20, and 24
weeks 4, 8, 12, 16, 20, and 24
Number of Subjects With ALT in Normal Range at Week 24
Time Frame: Week 24
Normal range is <40 U/L
Week 24
Maximum Observed Concentrations (Cmax)
Time Frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
Minimum Observed Concentration (Cmin)
Time Frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
Area Under Concentration-time (AUC)
Time Frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
Half-life
Time Frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Manal Abdelmalek

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Manal F Abdelmalek, MD, MPH, Duke University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 24, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 24, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 13, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 7, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 7, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00062677

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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